Резюме
Левицька Г.В., Путіенко О.О., Мохаммад Абдулхади. Характер змін інтерлейкіну-6 та фактора некрозу пухлини α у хворих на регматогенне відшарування сітківки, ускладнене відшаруванням судинної оболонки, після інтравітреального введення тріамцинолону ацетоніду.
У 23 хворих на регматогенне відшарування сітківки, ускладнене відшаруванням судинної оболонки, досліджена спрямованість і вираженість змін прозапальних цитокінів ІЛ-6 і ФНП-α до і після проведення передопераційної протизапальної терапії. В результаті інтравітреального введення тріамцинолону ацетату (4 мг відмитих кристалів препарату) в крові відзначено факт зниження концентрації ІЛ-6 і ФНП-α на 38,7 % і 36,7 %. У слізній рідині виявлені більш виражені зміни: вміст цитокінів знижено в 2 і 1,7 рази відповідно для ІЛ-6 і ФНП-α. Кореляційний аналіз встановив наявність прямого зв’язку між клінічними ознаками, що характеризують вираженість запального процесу та рівнем ІЛ-6 і ФНП-α у крові після лікування. У сльозі результати кореляційного аналізу показали наявність достовірного прямого зв’язку між рівнем ІЛ-6 після лікування і параметрами, що характеризують ступінь циліарной болісності та помутніння склоподібного тіла.
Ключові слова: регматогенне відшарування сітківки, відшарування судинної оболонки, інтерлейкін 6, фактор некрозу пухлини α, тріамцинолон.
Резюме
Левицкая Г.В., Путиенко А.А., Мохаммад Абдулхади. Характер изменений интерлейкина-6 и фактора некроза опухоли α у больных регматогенной отслойкой сетчатки, осложненной отслойкой сосудистой оболочки, после интравитреального введения триамцинолона ацетонида.
У 23 больных регматогенной отслойкой сетчатки, осложненной отслойкой сосудистой оболочки, исследована направленность и выраженность изменений провоспалительных цитокинов ИЛ-6 и ФНО-α до и после проведения предоперационной противовоспалительной терапии. В результате интравитреального введения триамцинолона ацетата (4 мг отмытых кристаллов препарата) в крови отмечен факт снижения концентрации ИЛ-6 и ФНО-α на 38,7% и 36,7%. В слезной жидкости выявлены более выраженные изменения: содержание цитокинов снижено в 2 и 1,7 раза соответственно для ИЛ-6 и ФНО-α. Корреляционный анализ установил наличие прямой связи между клиническими признаками, характеризующими выраженность воспалительного процесса и уровнем в крови ИЛ-6 и ФНО-α после лечения. В слезе результаты корреляционного анализа показали наличие достоверной прямой связи между уровнем ИЛ-6 после лечения и параметрами, характеризующими степень цилиарной болезненности и помутнения стекловидного тела.
Ключевые слова: регматогенная отслойка сетчатки, отслойка сосудистой оболочки, интерлейкин 6, фактор некроза опухоли α, триамцинолон.
Summary
Levytska G.V., Putienko A.A., Mohammad Abdulhadi. Interleukin-6 and tumor necrosis factor changes in patients with rhegmatogenous retinal detachment complicated by choroidal detachment after intravitreal triamcinolone acetonide injection.
In 23 patients with rhegmatogenous retinal detachment complicated by choroidal detachment direction and intensity of pro-inflammatory cytokines IL-6 and TNF α changes were investigated before and after preoperative anti-inflammatory therapy. Blood concentrations of IL-6 and TNF α decreased by 38.7% and 36.7% as a result of intravitreal triamcinolone acetate injection (4 mg of washed crystals). In tear fluid more expressed changes were revealed: cytokines level decreased in 2 times for IL-6 and 1.7 times for TNF α. Correlation analysis showed direct correlation between clinical symptoms characterizing inflammation severity and blood levels of IL-6 and TNF α after treatment. Correlation analysis showed the presence of significant direct correlation between IL-6 level in tears after treatment and parameters characterizing degree of ciliary pain and vitreous opacities.
Key words: rhegmatogenous retinal detachment, choroidal detachment, interleukin-6, tumor necrosis factor α, triamcinolone.
Рецензент: д.мед.н., проф. А.М. Петруня

УДК 617.735-007.281-06:617.723-007.281-07+577.11

ГУ «Институт глазных болезней и тканевой терапии им. В.П.Филатова НАМН Украины» (Одесса)

 SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine”  (Odessa)

g.levytskaya@mail.ru

dr_abdul5@bk.ru

Background. The relevance of rhegmatogenous retinal detachment (RRD) is defined as severity and high disability caused by this disease, as well as a frequency of occurrence (10 cases per 100,000 per year in patients with no ocular surgery or trauma history) [4].

RRD severity is defined by a number of factors: type, size, number and location of retinal breaks, state of the vitreous and presence of previous surgery. In addition, in some cases RRD is accompanied by complications development including proliferative vitreoretinopathy (PVR), inflammatory processes, oftalmohypotension. In 2-4.5% RRD is complicated by choroidal detachment (CD) which has a negative effect on the treatment results [7, 9, 11, 12]. Presence of uveal syndrome is peculiarity of the clinical manifestation of RRD complicated by CD, which manifests range of features characterizing inflammatory process.

It is known that immune system state is important to the development and outcome of detachment. Imbalance of cytokines coordinating cellular interactions under pathological conditions, regulating cell migration, activation and their conversion into effector cells eventually violates interrelation existing in a local system, contributing generalization of inflammatory process [5, 6].

However, studies of the immune disturbances role in the RRD mechanisms are not numerous and presented data remains controversial and ambiguous. According to that, preoperative anti-inflammatory therapy in order to reduce the risk of operational and post-operative complications in patients with RRD complicated by CD is justified and clinically proven.

Choroidal detachment elimination and relief of inflammatory process and consequently treatment prognosis improvement in RRD complicated by CD after preoperative systemic steroid therapy was noted in literature [10]. However, achieved functional results after achieved reattachment remained low mostly by increasing macular detachment duration conducted by preoperative therapy [8]. On our point of view in this case substantiated is the elimination of inflammatory component by intravitreal injection of triamcinolone acetonide (TA) prior to vitrectomy. After an appropriate treatment desired result was obtained: intraocular inflammation was eliminated in all patients, positive dynamics of IOP recovering, totally resolved ciliochoroidal detachment in the majority of cases (80.6%), in 19.4% patients CD decreased in size and prominence [3].

The aim of this work was to determine the nature of changes in expression of proinflammatory cytokines locally and systemically in patients with RRD complicated by CD as a result of preoperative intravitreal triamcinolone acetonide injection.

Materials and methods

We observed 23 patients (23 eyes) with RRD complicated by CD treated at the Vitreoretinal Surgery and Laser Department of SI "The Filatov Institute of eye diseases and tissue therapy of NAMS of Ukraine".with ROS, complicated retinal detachment of the choroid. Patient’s age ranged from 24 to 71 years, 9 (39.1%) men 14 (60.9%) women.

The average retinal detachment duration was 19.7 (11.4) days (range from 7 to 60 days). In 21 cases (91.3%) retinal detachment spread for 3 or more quadrants. Macula was detached in all eyes.

Choroidal detachment (by ultrasound scan on "Aviso" "Quantel Medical") was the entire circumference in 15 eyes (65.2%), extended on 3 quadrants in 6 cases (26.1%), on 2 – 2 eyes (8.7%). Detachment prominence ranged from 0.3 to 7.5 mm, on average - 4.1 (2.1) mm.

Mean detectable initial visual acuity was 0.02 (0.01) in 10 (43.5%) cases and correct light perception in 22 patients (43.5%).

In all cases there were intraocular inflammation signs. As the main symptom - ciliary pain was noted in 10 cases (43.5%), conjunctival injection - in 11 patients (47.8%), posterior synechiae presence in three or more quadrants - in 5 eyes (21.7%) and significant vitreous opacity - in 12 (52.2%).

Proinflammatory cytokines interleukin-6 and tumor necrosis factor ? (TNF ?) levels were measured in blood serum and tears using ELISA test systems "Vector-Best" Russia. Samples of biological material were taken at admission to the hospital before and after preoperative antiinflammatory therapy and after treatment. Blood and lacrimal fluid obtained by previously described scheme [2].

Preoperative inflammatory therapy performed by intravitreal injection of 4 mg washed crystals of TA [3].

Statistical analysis was performed using STATISTICA-8 package. Parametric t-test was used for pairwise comparison of two groups with a preliminary estimate of normality and the Spearman rank correlation coefficient [1]. Results are presented as mean values of cytokines concentrations and standard deviations in parentheses.

Results and discussion

According to this study preoperative preparation of RRD patients complicated by CD prior to vitrectomy by intravitreal TA ensured elimination of inflammation [3]. Direction and intensity of pro-inflammatory cytokines IL-6 and TNF ? changes were investigated to determine the mechanisms of positive action of TA in this group of patients.

It was found that IL-6 and TNF ? level in blood of RRD patients was within the normal range of healthy people according to instructions of relevant reagents sets. Preliminary studies showed that presence of concomitant CD complicating RRD course promotes a statistically significant increase of IL-6 and TNF ? level in the blood and tears fluid. Data analysis according to severity of inflammation showed an increase in cytokines levels in patients with greater degree of ciliary pain, severe conjunctival injection, prevalence of posterior synechiae, severe vitreous opacities [2].

Analysis of IL-6 and TNF ? levels in patients with CD after anti-inflammatory therapy showed: significant reduction of cytokines from baseline in blood by 38.7% and 36.7% what confirm therapeutic effect of intravitreal TA and reduction in 2 times for IL-6 and 1.7 times for TNF ? in tears which also confirms the pathogenetic direction of therapy and appropriateness of the local (intravitreal) administration of TA (Table 1, Fig. 1). Furthermore, the fact of more expressed reduction of local levels of IL-6 TNF ? probably indicates that predominant cytokine production into eye.

Table 1

Cytokine levels in patients with rhegmatogenous retinal detachment with choroidal detachment after anti-inflammatory therapy (pg / ml)

To reveal links between clinical signs of intraocular inflammation and baseline levels of cytokines data was analyzed using Spearman's rank correlation coefficient. Corresponding results are shown in Table 2.

Correlation analysis shown a direct strong significant link between baseline levels of IL-6 and TNF ? in the blood and the degree of consideration of clinical signs of inflammation, indicating increased levels of this factor with a strong inflammatory component that accompanies the disease.

Correlation between the initial content of cytokines in tear fluid of patients and severity intraocular inflammation was an interesting study. The results showed the presence of reliable direct correlation between IL-6 level in tear fluid and following features: ciliary pain, severity of vitreous opacities and presence of conjunctival injection. For TNF ? level in tear fluid significant correlation was noted only with ciliary pain severity and vitreous opacities degree.

No significant correlation was found between baseline IL-6 and TNF  in tear fluid and synechiae presence (Table 2) which is probably due to the suppression of pro-inflammatory cytokines in existence for a long period of retinal detachment in these cases, with developed anterior uveitis and ended with the formation of synechiae.

Table 2

The rank correlation between the clinical characteristics of rhegmatogenous retinal detachment complicated by detachment choroid and IL-6 and TNF ? levels in the blood and tears of patients before treatment

Considering that RRD complicated by CD treatment has high rate of postoperative complications caused by the initial inflammation [7,9,10], it seems appropriate to study features of cytokine levels changes after treatment. We have previously found that intravitreal TA can eliminate signs of intraocular inflammation [3]. The positive disease dynamics is accompanied by statistically significant reductions of IL-6 and TNF ? levels in blood and tear fluid (Table 1). Despite this, cytokines levels in the blood prior to vitrectomy showed presence of a strong significant correlation with all clinical signs of intraocular inflammation. In tears after anti-inflammatory treatment was a significant correlation between IL-6 and parameters characterizing degree of ciliary pain and vitreous opacities (Table 3).

Table 3

The rank correlation between the clinical characteristics of rhegmatogenous retinal detachment complicated by detachment choroid and IL-6 and TNF ? levels in the blood and tears of patients after treatment

Obtained data indicate the need for targeted immunomodulation, which should take place either in the preoperative preparation of the RRD complicated by CD patients. First of all, this early suppression of local and systemic inflammatory immunomediators hypersecretion.

Conclusion.

Summarizing analysis results, we can conclude important role of proinflammatory cytokines IL-6 and TNF ? in inflammatory response development in RRD complicated by CD cases. And ability of immunocorrection by intravitreal corticosteroid therapy (4 mg triamcinolone acetonide) as preoperative preparation prior to vitrectomy.

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